title: The antioxidant tempol decreases acute pulmonary thromboembolism-induced hemolysis and nitric oxide consumption.
abstract: BACKGROUND
  Acute pulmonary thromboembolism (APT) is a critical condition associated with acute pulmonary hypertension. Recent studies suggest that oxidative stress and hemolysis contribute to APT-induced pulmonary hypertension, possibly as a result of increased nitric oxide (NO) consumption. We hypothesized that the antioxidant tempol could attenuate APT-induced hemolysis, and therefore attenuate APT-induced increases in plasma NO consumption.
  
  
  METHODS
  APT was induced in anesthetized sheep with autologous blood clots. The hemodynamic effects of tempol infused at 1.0mg/kg/min 30 min after APT were determined. Hemodynamic measurements were carried out every 15 min. To assess oxidative stress, serum 8-isoprostanes levels were measured by ELISA. Plasma cell-free hemoglobin concentrations and NO consumption by plasma samples were determined. An in vitro oxidative AAPH-induced hemolysis assay was used to further validate the in vivo effects of tempol.
  
  
  RESULTS
  APT caused pulmonary hypertension, and increased pulmonary vascular resistance in proportion with the increases in 8-isoprostanes, plasma cell-free hemoglobin concentrations, and NO consumption by plasma (all P<0.05). Tempol attenuated the hemodynamic alterations by approximately 15-20% and blunted APT-induced increases in 8-isoprostanes, in cell-free hemoglobin concentrations, and the increases in NO consumption by plasma (P<0.05). Tempol dose-dependently attenuated AAPH-induced in vitro hemolysis (P<0.05).
  
  
  CONCLUSIONS
  Our findings are consistent with the idea that antioxidant properties of tempol decrease APT-induced hemolysis and nitric oxide consumption, thus attenuating APT-induced pulmonary hypertension.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo.
authors.forename: Ozelia
authors.initials: O
authors.lastname: Sousa-Santos
authors.forename: Evandro M
authors.initials: EM
authors.lastname: Neto-Neves
authors.forename: Karina C
authors.initials: KC
authors.lastname: Ferraz
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Sertório
authors.forename: Rafael L
authors.initials: RL
authors.lastname: Portella
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D018384:Oxidative Stress / Q000187:drug effects; D011655:Pulmonary Embolism / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D012756:Sheep; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D009569:Nitric Oxide; C001803:tempol
keywords: Acute pulmonary thromboembolism; Antioxidant; Hemoglobin; Hemolysis; Nitric oxide consumption; Oxidative stress; Tempol